Direct Parameter Fitting of Action Potentials in Skeletal Muscle Cells Which Include Longitudinal Segments
Brent Foy, Ph.D. (Advisor); Mark M. Rich, M.D., Ph.D. (Committee Member); Amit Sharma, Ph.D. (Committee Member)
Master of Science (MS)
Excitation of skeletal muscle cells triggers a large voltage spike known as an action potential (AP), leading to muscle contraction. Modeling of an AP is typically done using the method developed by scientists Hodgkin and Huxley (HH). In the HH method, voltage and time gated Na+ and K+ ionic currents are simulated, along with a positive “Leak” ionic current and capacitive current. Due to the complexity and the computational time required for simulation, direct fitting of HH parameters to experimental APs has rarely been attempted. A previous thesis at Wright State performed direct fitting for the case of a single compartment muscle cell. This study will introduce propagation to the existing model by adding small longitudinal segments simulating the currents flowing and triggering APs in later portions of the cell. If no adjustments to the single compartment HH parameters are made, adding increasing longitudinal segments leads to a very poor simulation of the AP shape. The simulated AP is too wide, and the peak voltage is too low. However, very few clear links between the number of segments and changes in specific HH parameter values were identified. Each parameter was found to vary by at least a factor of 2 between similar data sets. It is clear that multiple parameter sets are allowable, obscuring direct links between segments and parameter values. In order to further understand the robustness of the found parameter sets and to identify what regions of parameter space is allowable in order to achieve a well fit AP a confidence interval test was completed. Scanning through each parameter and fitting the rest revealed that each of α_h_bar, β_h_bar, kβh, V_n_bar, kαn, α_n _bar, β_n_bar, and Na permeability hold a well-defined interval in which near perfect fits can be found. While for kαh, kβn, and kβm no upper-bound was identified, and for K permeability, V_h_bar, kαm, β_m_bar, α_m_bar, V_m_bar the patterns where unclear.
Department or Program
Department of Physics
Year Degree Awarded
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